Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome

Background Temple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal expressed genes and a silencing the paternally expressed genes in the 14q32 imprinted domain. Classical TS14 phenotypic fe...

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Autores: Baena, Neus, Monk, David, Aguilera, Cinthia, Fraga, Mario F., Fernández, Agustín F., Gabau, Elisabeth, Corripio, Raquel, Capdevila, Nuria, Trujillo, Juan Pablo, Ruiz, Anna, Guitart, Miriam
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/214371
Acceso en línea:https://hdl.handle.net/2445/214371
Access Level:acceso abierto
Palabra clave:Metilació
Expressió gènica
Malalties rares
Methylation
Gene expression
Rare diseases
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spelling Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndromeBaena, NeusMonk, DavidAguilera, CinthiaFraga, Mario F.Fernández, Agustín F.Gabau, ElisabethCorripio, RaquelCapdevila, NuriaTrujillo, Juan PabloRuiz, AnnaGuitart, MiriamMetilacióExpressió gènicaMalalties raresMethylationGene expressionRare diseasesBackground Temple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal expressed genes and a silencing the paternally expressed genes in the 14q32 imprinted domain. Classical TS14 phenotypic features include pre- and postnatal short stature, small hands and feet, muscular hypotonia, motor delay, feeding difficulties, weight gain, premature puberty along and precocious puberty. Methods An exon array comparative genomic hybridization was performed on a patient affected by psychomotor and language delay, muscular hypotonia, relative macrocephaly, and small hand and feet at two years old. At 6 years of age, the proband presented with precocious thelarche. Genes dosage and methylation within the 14q32 region were analyzed by MS-MLPA. Bisulfite PCR and pyrosequencing were employed to quantification methylation at the four known imprinted differentially methylated regions (DMR) within the 14q32 domain: DLK1 DMR, IG-DMR, MEG3 DMR and MEG8 DMR. Results The patient had inherited a 69 Kb deletion, encompassing the entire DLK1 gene, on the paternal allele. Relative hypermethylation of the two maternally methylated intervals, DLK1 and MEG8 DMRs, was observed along with normal methylation level at IG-DMR and MEG3 DMR, resulting in a phenotype consistent with TS14. Additional family members with the deletion showed modest methylation changes at both the DLK1 and MEG8 DMRs consistent with parental transmission. Conclusion We describe a girl with clinical presentation suggestive of Temple syndrome resulting from a small paternal 14q32 deletion that led to DLK1 whole-gene deletion, as well as hypermethylation of the maternally methylated DLK1-DMR.Springer Science and Business Media LLC2024202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion11 p.application/pdfhttps://hdl.handle.net/2445/214371Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1186/s13148-024-01652-8Clinical Epigenetics, 2024, vol. 16, num. 1https://doi.org/10.1186/s13148-024-01652-8cc by (c) Baena, Neus et al., 2024http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2143712026-05-29T05:05:01Z
dc.title.none.fl_str_mv Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
title Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
spellingShingle Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
Baena, Neus
Metilació
Expressió gènica
Malalties rares
Methylation
Gene expression
Rare diseases
title_short Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
title_full Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
title_fullStr Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
title_full_unstemmed Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
title_sort Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome
dc.creator.none.fl_str_mv Baena, Neus
Monk, David
Aguilera, Cinthia
Fraga, Mario F.
Fernández, Agustín F.
Gabau, Elisabeth
Corripio, Raquel
Capdevila, Nuria
Trujillo, Juan Pablo
Ruiz, Anna
Guitart, Miriam
author Baena, Neus
author_facet Baena, Neus
Monk, David
Aguilera, Cinthia
Fraga, Mario F.
Fernández, Agustín F.
Gabau, Elisabeth
Corripio, Raquel
Capdevila, Nuria
Trujillo, Juan Pablo
Ruiz, Anna
Guitart, Miriam
author_role author
author2 Monk, David
Aguilera, Cinthia
Fraga, Mario F.
Fernández, Agustín F.
Gabau, Elisabeth
Corripio, Raquel
Capdevila, Nuria
Trujillo, Juan Pablo
Ruiz, Anna
Guitart, Miriam
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Metilació
Expressió gènica
Malalties rares
Methylation
Gene expression
Rare diseases
topic Metilació
Expressió gènica
Malalties rares
Methylation
Gene expression
Rare diseases
description Background Temple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal expressed genes and a silencing the paternally expressed genes in the 14q32 imprinted domain. Classical TS14 phenotypic features include pre- and postnatal short stature, small hands and feet, muscular hypotonia, motor delay, feeding difficulties, weight gain, premature puberty along and precocious puberty. Methods An exon array comparative genomic hybridization was performed on a patient affected by psychomotor and language delay, muscular hypotonia, relative macrocephaly, and small hand and feet at two years old. At 6 years of age, the proband presented with precocious thelarche. Genes dosage and methylation within the 14q32 region were analyzed by MS-MLPA. Bisulfite PCR and pyrosequencing were employed to quantification methylation at the four known imprinted differentially methylated regions (DMR) within the 14q32 domain: DLK1 DMR, IG-DMR, MEG3 DMR and MEG8 DMR. Results The patient had inherited a 69 Kb deletion, encompassing the entire DLK1 gene, on the paternal allele. Relative hypermethylation of the two maternally methylated intervals, DLK1 and MEG8 DMRs, was observed along with normal methylation level at IG-DMR and MEG3 DMR, resulting in a phenotype consistent with TS14. Additional family members with the deletion showed modest methylation changes at both the DLK1 and MEG8 DMRs consistent with parental transmission. Conclusion We describe a girl with clinical presentation suggestive of Temple syndrome resulting from a small paternal 14q32 deletion that led to DLK1 whole-gene deletion, as well as hypermethylation of the maternally methylated DLK1-DMR.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/214371
url https://hdl.handle.net/2445/214371
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s13148-024-01652-8
Clinical Epigenetics, 2024, vol. 16, num. 1
https://doi.org/10.1186/s13148-024-01652-8
dc.rights.none.fl_str_mv cc by (c) Baena, Neus et al., 2024
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Baena, Neus et al., 2024
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11 p.
application/pdf
dc.publisher.none.fl_str_mv Springer Science and Business Media LLC
publisher.none.fl_str_mv Springer Science and Business Media LLC
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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